4.4 Article

1,3,5,8-Tetrahydroxyxanthone suppressed adipogenesis via activating Hedgehog signaling in 3T3-L1 adipocytes

Journal

FOOD SCIENCE AND BIOTECHNOLOGY
Volume 31, Issue 11, Pages 1473-1480

Publisher

KOREAN SOCIETY FOOD SCIENCE & TECHNOLOGY-KOSFOST
DOI: 10.1007/s10068-022-01130-y

Keywords

Adipogenesis; 1; 3; 5; 8-Tetrahydroxyxanthone; Hedgehog signaling; Gli1

Funding

  1. National Research Foundation of Korea [NRF-2021R1F1A1063279]
  2. Bio-Synergy Research Project of the Ministry of Science, ICT, and Future Planning [NRF-2013M3A9C4078156]
  3. Chung-Ang University Graduate Research Scholarship (Academic Scholarship for the College of Biotechnology and Natural Resources)

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In this study, the researchers investigated the effect of 1,3,5,8-tetrahydroxyxanthone (THX) on the adipogenesis of 3T3-L1 adipocytes. They found that THX inhibited lipid accumulation and reduced the protein levels of key adipogenic transcriptional factors. They also discovered that THX enhanced the activity of the Hedgehog signaling pathway, leading to the suppression of fat formation. These findings suggest that THX may be a potential agent for the prevention of obesity.
In this study, we investigated the effect of 1,3,5,8-tetrahydroxyxanthone (THX) on the adipogenesis of 3T3-L1 adipocytes. THX, a xanthone isolated from Gentianella acuta, inhibited lipid accumulation in 3T3-L1 adipocytes and reduced the protein levels of the key adipogenic transcriptional factors, peroxisome proliferator-activated receptor gamma (PPAR gamma) and CCAAT/enhancer-binding protein alpha (C/EBP alpha), in a dose-dependent manner. In addition, THX enhanced the transcriptional activity of Gli1 known as the key indicator of Hedgehog (Hh) signaling activity and increased the expression of Gli1 and its upstream regulator Smo. The Smo activator SAG exerted the similar effect with THX on regulating Gli1, Smo, PPAR gamma and C/EBP alpha expression, which led to the suppression of fat formation in 3T3-L1 adipocytes. Furthermore, we found that the inhibitory effect of THX on adipogenesis was derived from regulation of the early stage of adipogenesis. These results suggest that THX suppresses the differentiation of adipocyte through Hh signaling and may be considered as a potent agent for the prevention of obesity.

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